The safety of silver amalgam as a dental restorative material has been controversial since its introduction 150 years ago, but-until recently it has been generally assumed that the exposure to mercury from dental amalgam is limited to the acute placement phase. Some recent studies (mostly observational and primarily of adults) have demonstrated chronic release of mercury vapor from amalgam fillings during chewing and brushing, raising new safety concerns. The randomized trial, Children's Amalgam Trial (CAT) is designed as a comprehensive assessment of the relative safety of silver amalgam, compared to the alternate, mercury-free materials, demonstrating equivalence of cognitive and renal outcomes. Children aged 6-10 at last birthday with no prior dental restoration (to minimize prior mercury exposure) and mixed (primary and permanent) dentition were recruited from two New England communities (rural Main and inner city Boston/Cambridge, Massachusetts) to represent, to the extent feasible, the likely effects in children in the US. Children were chosen for this trial as they are most likely to be amalgam-free at randomization and, given their smaller body mass and developmental stage, more likely to demonstrate adverse effects (if any) of increased body mercury burden. This 5-year competing continuation will enable completion of 6 years of observation of the trial subjects/randomized from August 1997 to September 1999). Current funding, through July 2001, will include two years of observation only. Given the obvious public health significance of the potential long range impact of mercury on cognitive function, the primary endpoint measure is the full scale IQ score of the Wechsler Intelligence Scale for Children: Third Edition (WISC III) and the primary outcome is the estimated change in the score between Baseline and 6 years post randomization, adjusted for the baseline IQ score. Secondary outcomes include more immediately measured safety endpoints that will be monitored annually, including: urine mercury levels; a dip-stick screening test for urinary protein (confirmed by albumin level); and gamma-glutamyl transpeptidase (gamma-GTP). Other endpoints include other aspects of cognitive function from an extensive neuropsychological test battery, while key covariates include a measure of dietary mercury (hair levels) and the dose of amalgam summarized in "surface-years" of exposure. To date, 534 subjects have been randomized (107%) and follow-up through the 12 month visit, although not yet complete, indicates that the initial (12 month) response rate should be at least 92%. Subsequent losses are expected to be negligible (about 2% per year). A non- orthogonal analysis of covariance will test for equivalence on IQ scores between treatments arms similar modeling will be used to address secondary aims.